Extended release tablet and method for making and using same

ABSTRACT

Provided are cap layer compositions and base layer compositions, providing quick and extended release of an active ingredient, respectively, when placed in water. Further provided are dual release compositions including a base composition and a cap composition. The base composition may include a plaster and an active agent, and it may further include at least one of a water-soluble binder, a non-water-soluble binder, and a lubricant. The cap composition may include a plaster and an active agent, and it may further include at least one of a disintegrating agent, a non-water-soluble binder, and a lubricant. The compositions may be heated and mixed and formed into a tablet. Further provided are methods of making the compositions. Further provided are methods of controlling or eliminating pests and methods of increasing the potability of water. The compositions are effective for controlling or eliminating pests such as mosquitoes when applied at an application site.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 12/533,937filed Jul. 31, 2009, which claims priority to U.S. ProvisionalApplication No. 61/085,315 filed Jul. 31, 2008, and U.S. ProvisionalApplication No. 61/093,054 filed Aug. 29, 2008, each of which areincorporated herein by reference in their entirety.

FIELD OF USE

This invention relates to extended release tablets, and particularly,their use in pest control applications. It also relates to dual releasetablets containing active ingredient in an immediate release matrix andactive ingredient in an extended release matrix. The invention alsorelates to methods of making dual release and extended release tablets.

BACKGROUND

Over the years, considerable effort has been expended to control pest(e.g., mosquito) populations. Pest control tablets that can provide anextended release of a pest control composition are desirable.

SUMMARY

In one aspect the invention provides a method for forming a compositioncomprising mixing without adding water at least one active agent, aplaster, and a binder, wherein the composition provides an extendedrelease of the active agent over a period of at least 30 days whenplaced in water.

In another aspect, the invention provides a method for forming acomposition comprising mixing without adding water at least one activeagent, a plaster, and a binder, wherein the composition provides a quickrelease of the active agent over a period of less than 10 minutes whenplaced in water.

In another aspect, the invention provides a dual-release compositioncomprising a cap composition comprising at least one active agent and aplaster, and a base composition comprising at least one active agent anda plaster. The cap composition may provide a quick release of the activeagent over a period of less than 10 minutes, and the base compositionmay provide an extended release of the active agent over a period of atleast 30 days when placed in water.

In another aspect, the invention provides a tablet comprising a plasterand at least one active agent selected from the group consisting of apesticide, insecticide, herbicide, fungicide, nematicide, acaricide,bactericide, rodenticide, miticide, algicide, germicide, repellant, andnutrient.

In another aspect, the invention provides a method of making an extendedrelease solid matrix, wherein the method comprises mixing at least oneactive agent, a plaster, and a binder to form a mixture, heating themixture at about 40° C. to about 75° C., and cooling the mixture. Themethod may further comprise breaking up the cooled mixture into granulesand compressing the granules into a tablet.

DETAILED DESCRIPTION

Before any embodiments of the invention are explained in detail, it isto be understood that the invention is not limited in its application tothe details of construction and the arrangement of components set forthin the following description or illustrated in the following drawings.The invention is capable of other embodiments and of being practiced orof being carried out in various ways. Also, it is to be understood thatthe phraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including,” “comprising,” or “having” and variations thereof herein ismeant to encompass the items listed thereafter and equivalents thereofas well as additional items. Unless specified or limited otherwise, theterms “mounted,” “connected,” “supported,” and “coupled” and variationsthereof are used broadly and encompass both direct and indirectmountings, connections, supports, and couplings. Further, “connected”and “coupled” are not restricted to physical or mechanical connectionsor couplings.

It also is understood that any numerical range recited herein includesall values from the lower value to the upper value. For example, if aconcentration range is stated as 1% to 50%, it is intended that valuessuch as 2% to 40%, 10% to 30%, or 1% to 3%, etc., are expresslyenumerated in this specification. These are only examples of what isspecifically intended, and all possible combinations of numerical valuesbetween and including the lowest value and the highest value enumeratedare to be considered to be expressly stated in this application.

In one aspect, the invention may provide a composition comprising atleast one of a cap composition and a base composition. The capcomposition may comprise at least one of an active ingredient, adisintegrating agent, a plaster, a water-soluble binder, a non-watersoluble binder, a lubricant, and combinations thereof. The basecomposition may comprise at least one of an active ingredient, aplaster, a water-soluble binder, a non-water soluble binder, alubricant, and combinations thereof. The cap composition may provide aquick release of the active ingredient and the base composition mayprovide an extended release of the active ingredient. The capcomposition and the base composition may be in tablet form.

In another aspect, the invention may provide a composition comprising atleast one of an active ingredient, a plaster, a water-soluble binder, anon-water soluble binder, a lubricant, and combinations thereof. Thecomposition may provide an extended release of the active ingredientover a period of time. The composition may be in tablet form.

In another aspect, the invention may provide a composition comprising atleast one of an active ingredient, a plaster of Paris, a polyethyleneglycol, a non-water soluble binder, a lubricant, and combinationsthereof. The composition may provide an extended release of the activeingredient over a period of time. The composition may be in tablet form.

In a further aspect, the invention may provide a composition comprisingat least one of an active ingredient, a disintegrating agent ordisintegrant, a plaster, a water-soluble binder, non-water solublebinder, and combinations thereof. The composition may further comprise alubricant. The composition may provide a quick release of the activeingredient. The composition may be in tablet form.

In yet another aspect, the invention may provide a method of making acomposition that comprises blending an active ingredient, a plaster, awater-soluble binder, and a non-water soluble binder to form a mixture.The mixture may be heated to about 40° C. to about 75° C. until themixture granulates to form granules. The mixture may also be mixedduring heating. In another aspect, the mixture may be heated until about60° C. to about 65° C. until the mixture granulates. In another aspect,the mixture may be heated to about 40° C. to about 75° C. and form apliable mass. The pliable mass may be forced through an extruder andcooled, and the extrudates may be broken into granules. The pliable massmay be cooled and become hard, and the hard mass may be broken intogranules. The granules may also be screened for a particle size fromabout −20 mesh to about +60 mesh and then compressed into a tablet.

In another aspect, the invention may provide a composition comprising atleast one of an active ingredient, a water-soluble binder, and aplaster. The active ingredient, the water-soluble binder, and theplaster may form a matrix. The matrix may provide extended release ofthe active ingredient over a period of time. The composition may alsocomprise a non-water soluble binder. The non-water soluble binder mayact to slow down the rate the matrix dissolves. The composition may bein tablet form.

In yet another aspect, the invention may provide a compositioncomprising at least one of an active ingredient, a polyethylene glycol,and a plaster of Paris. The active ingredient, the polyethylene glycol,and the plaster of Paris may form a matrix. When the composition isplaced in water, the polyethylene glycol may dissolve and the plaster ofParis may hydrolyze into gypsum, forming a gypsum matrix thatincorporates the active ingredient. The gypsum matrix may hold its shapeand provide an extended release of the active ingredient over a periodof time. The composition may also comprise a non-water soluble binder.The non-water soluble binder may act to slow down the rate the matrixdissolves. The composition may be in tablet form.

In one embodiment, the invention may provide a dual release compositioncomprising a cap composition or top layer and a base composition orbottom layer. The cap composition and base composition may havedifferent release rate characteristics. The dual release composition maybe in tablet form.

The cap composition may comprise a quick release matrix which maycomprise at least one of an active ingredient, a disintegrating agent, aplaster, a non-water soluble binder, a water-soluble binder, alubricant, and combinations thereof. The composition may provide a quickrelease of active ingredient and subsequent initial control. The basecomposition may comprise an extended release matrix which may compriseat least one of an active ingredient, a plaster, a water soluble binder,a non-water soluble binder, a lubricant and combinations thereof. Thebase composition may provide extended release of active ingredient overa period of time.

In another embodiment, the invention may provide an extended releasecomposition comprising an active ingredient, a plaster, a water solublebinder, a non-water soluble binder, a lubricant and combinationsthereof. This tablet may provide an extended release over a period oftime. The extended release composition may be in tablet form.

In a further embodiment, the invention may provide a quick releasecomposition comprising at least one of an active ingredient, adisintegrating agent, a plaster, a non-water soluble binder,water-soluble binder, a lubricant, and combinations thereof. Thecomposition may provide a quick release of active ingredient. The quickrelease composition may be in tablet form.

As used herein, the term “quick release” means that the release ofactive ingredient from the tablet when the tablet is placed in water mayoccur over periods of less than about 10 minutes, particularly less thanabout 5 minutes, and more particularly less than about 3 minutes.Suitably, the release of the active agent is complete within about 10minutes, particularly within about 5 minutes, and more particularlywithin about 3 minutes.

As used herein, the term “extended release composition” or “extendedrelease” means that the release of active ingredient from the tabletwhen the tablet is placed in water may occur over periods of at leastabout 30 days, at least about 60 days, at least about 90 days, or atleast about 150 days. If the extended release composition is in tabletform, the tablet may be hard enough to slowly release active ingredientover a period of time.

Active ingredients may include, but are not limited to, pesticides,insecticides, herbicides, fungicides, nematicides, acaricides,bactericides, rodenticides, miticides, algicides, germicides,repellents, nutrients, and combinations thereof. Specific examples ofinsecticides include, but are not limited to, a botanical, a carbamate,a microbial, a dithiocarbamate, an imidazolinone, an organophosphate, anorganochlorine, a benzoylurea, an oxadiazine, a spinosyn, a triazine, acarboxamide, a tetronic acid derivative, a triazolinone, aneonicotinoid, a pyrethroid, a pyrethrin, and a combination thereof.Specific examples of herbicides include, without limitation, a urea, asulfonyl urea, a phenylurea, a pyrazole, a dinitroaniline, a benzoicacid, an amide, a diphenylether, an imidazole, an aminotriazole, apyridazine, an amide, a sulfonamide, a uracil, a benzothiadiazinone, aphenol, and a combination thereof. Specific examples of fungicidesinclude, without limitation, a dithiocarbamate, a phenylamide, abenzimidazole, a substituted benzene, a strobilurin, a carboxamide, ahydroxypyrimidine, a anilopyrimidine, a phenylpyrrole, a steroldemethylation inhibitor, a triazole, and a combination thereof. Specificexamples of acaricides or miticides include, without limitation,rosemary oil, thymol, spirodiclogen, cyflumetofen, pyridaben,diafenthiuron, etoxazole, spirodiclofen, acequinocyl, bifenazate, and acombination thereof. The tablets according to the invention may comprisean effective amount of the active agent. As used herein, “effectiveamount” means a quantity of a compound sufficient enough to provide asignificant modification at an application site, for example,significant elimination of pests.

Plasters may include, but are not limited to, plaster of Paris, limeplaster, cement plaster, and combinations thereof. Specific examples ofplasters include, without limitation, Terra Alba, Snow White Filler,Puritan Pottery Plaster, No. 1 Moulding Plaster, No. 2 Moulding Plaster,Duramold Pottery Plaster, C-Base Plaster, Hydrocal A-11, Hydrocal B-11,Hydrocal X-21 MC, No. 1 Casting Plaster, Dental Plaster, CastingPlaster, Potting Plaster, Ultracal 30 Gypsum Cement, Ultracal 60 GypsumCement (all available from United States Gypsum), and combinationsthereof.

Water-soluble binders may include, without limitation, acaia, gelatin,tragacanth, sucrose, guar gum, bentonite, methylcellulose,carboxymethylcellulose, microcrystalline cellulose,polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyethyleneglycols of varying molecular weights, salts of alginic acid, lignins,and combinations thereof. Specific examples of polyethylene glycolsinclude polyethylene glycols with molecular weights in the range fromabout 1000 to about 8500, which include Carbowax 3350, Carbowax 4000,Carbowax 6000, Carbowax 8000, and combinations thereof.

Non-water soluble binders may include, without limitation, corn starch,pregelatinized starch, alginate, ethylcellulose, hydroxypropylcellulose,hydroxypropylmethylcellulose, polymethacrylate, dicalcium phosphatedihydrate, glyceryl behapate, and combinations thereof.

Disintegrants may include, without limitation, starch (corn, potato,wheat), pregelatinized starch, modified corn starch, sodium starchglycolate, citric acid, sodium bicarbonate, microcrystalline cellulose,gums (agar, guar, locust bean, pectin, tragacanth), croscarmellosesodium, alginic acid, resins, clays, surfactants, and combinationsthereof. The disintegrant may be an effervescent.

Lubricants may include, without limitation, hydrogenated vegetable oils,mineral oil, talc, stearic acid, metallic stearates such as magnesiumstearate, lauryl sulfate salts, boric acid, sodium chloride, sodiumbenzoate, sodium acetate, sodium oleate, polyethylene glycol, glycerylbehapate, and combinations thereof.

For the dual release composition, the amount of active ingredient in thebase composition may be from about 0.01% to about 50% by weight,particularly about 0.1% to about 25% by weight, more particularly about0.5% to about 12% by weight.

For the dual release composition, the amount of plaster in the basecomposition may be from about 40% to about 90% by weight, particularlyabout 50% to about 85% by weight, more particularly about 60% to about85% by weight.

For the dual release composition, the amount of water-soluble binder inthe base composition may be from about 5% to about 50% by weight,particularly about 5% to about 30% by weight, more particularly about 8%to about 20% by weight.

For the dual release composition, the amount of non-water soluble binderin the base composition may be from about 0% to about 30% by weight,particularly about 0% to about 20% by weight, more particularly about 0%to about 5% by weight.

For the dual release composition, the amount of lubricant added to thebase composition post granulation may be from about 0% to about 1.5% byweight, particularly about 0.1% to about 1% by weight, more particularlyabout 0.4% to about 1% by weight.

For the dual release composition, the amount of active ingredient in thecap composition may be from about 0.01% to about 30% by weight,particularly about 0.1% to about 20% by weight, more particularly about0.5% to about 10% by weight.

For the dual release composition, the amount of plaster in the capcomposition may be from about 0% to about 40% by weight, particularlyabout 5% to about 30% by weight, more particularly about 10% to about20% by weight.

For the dual release composition, the amount of disintegrate in the capcomposition may be from about 20% to about 80% by weight, particularlyabout 35% to about 80% by weight, more particularly about 50% to about75% by weight.

For the dual release composition, the amount of non-water soluble binderin the cap composition may be from about 2% to about 40% by weight,particularly about 5% to about 30% by weight, more particularly about 8%to about 15% by weight.

For the extended release composition, the amount of active ingredientmay be from about 1.0% to about 50% by weight, particularly about 3% toabout 30% by weight, more particularly about 5% to about 10% by weight.

For the extended release composition, the amount of plaster may be fromabout 40% to about 90% by weight, particularly about 50% to about 85% byweight, more particularly about 60% to about 85% by weight.

For the extended release composition, the amount of water-soluble bindermay be from about 5% to about 50% by weight, particularly about 5% toabout 30% by weight, more particularly about 8% to about 20% by weight.

For the extended release composition, the amount of lubricant added tothe composition post granulation may be from about 0% to about 1.5% byweight, particularly about 0.1% to about 1% by weight, more particularlyabout 0.4% to about 1% by weight.

It was unexpectedly discovered that a controlled release compositioncomprising a binder (e.g. polyethylene glycol), a plaster (e.g., gypsumcement), an active agent, and optionally other solid excipients may becreated without the use of water. The compositions and tablets of thepresent application may be prepared using different methods.

In one embodiment, the composition is prepared by first blending theingredients described above to form a mixture. Suitably, the ingredientsmay be combined without adding water to the mixture. The mixture may benon-aqueous. The ingredients may be combined and mixed without theaddition of water. When components of the invention are being mixed,“mixing without adding water” means the components are mixed whileadding substantially no water. While some water may or may notinherently be present in the components being mixed, substantially nowater is intentionally added. “Substantially no water” means no water orwater in a nominal amount. A nominal amount is an amount insufficient torender a resulting mixture a wet blend. Mixing without adding water maycomprise dry-blending the ingredients. The composition may be formed bydry-granulation. The mixture may be in a powder form. The ingredientsmay be blended in varying order (see the examples below).

In one embodiment, the mixture may be directly compressed into a tablet.To form tablets by direct compression, the ingredients may be combinedwithout the addition of water to form a dry mixture that may becompressed without heating to form a tablet.

In another embodiment, the ingredients or mixture may be processed withheat. The ingredients may or may not be mixed before and/or duringheating. Different equipment may be used for mixing and heating,including, but not limited to, blenders, paddle blenders, ribbonblenders, agitators, and extruders. The ingredients may be mixed andheated to from about 40° C. to about 75° C., particularly from about 50°C. to about 70° C., and more particularly from about 60° C. to about 65°C. The temperature may be adjusted depending on active ingredienttemperature limits and the melting point of the ingredients.

Heat may be applied in a variety of ways. For example, the ingredientsor mixture may be placed into a mixing container equipped with heatingtapes around the outside of the container. Alternatively, the mixturemay be placed in a rotating can and heat may be applied with a hand-heldheat gun. Heating of the mixture provides an unexpected way to granulatethe powders without the addition of water.

In one embodiment, with a combination of heat and intimate mixing usingvarying mixing cycles and times (see the examples below), the mixturemay granulate without the addition of any liquids. The mixture may beheated and mixed until the mixture granulates to form individualgranules. Heat and mechanical force may be applied to the mixture toform granules before the mixture is cooled. Suitably, the mixture may beheated to about 40° C. to about 70° C.

Granulation may involve the process of particle size enlargement wherethe mixture (in the form of a powder) is gathered together into larger,permanent aggregates whereby the aggregates become free-flowing. Thesegranules may improve the flow of the mixture and enhance itscompressibility.

In another embodiment, the mixture may be heated and form granules andcontinue to be heated past the granule stage to form a pliable solidmass or mixture and then forced under pressure through an orifice platewith specific diameter holes to form extrudates. The extrudates may coolquickly upon being extruded. The extrudates may be in the form of long,fine strands, which may be broken into granules. In one example theextrudates form about 0.7 mm diameter strands. Additionally, thediameter of the strand may be from about 0.6 mm to about 1.2 mm,depending on the selection of the diameter of the holes on the orificeplate.

In another embodiment, the mixture may be heated and form granules andcontinue to be heated past the granule stage to form a pliable solidmass or mixture. Upon cooling the pliable solid mass or mixture maybecome very hard. In order to use the mass, it may be broken up withforce to form granules (for instance, a hammer can be used).

If the mixture forms granules or extrudates, portions can be milledthrough a Wiley mill, a hammer mill, a knife-type mill, or anoscillating mill. Milling may be used, but it may not be required. Thegranules or milled material from the pliable solid mass may be screenedusing a 10, 20, 30, 40, 50, and/or 60 mesh sieve. The desired particlesize may then be selected to form a final granule mixture. The finalgranule mixture may be placed into a mixer. A lubricant may be added tocoat the surface of the granules to prevent them from sticking to thedie in the tablet press.

The different sieve fractions of granules may be compressed into atablet. The 40 mesh sieve fraction may be used for a uniform-lookingtablet. Alternatively, the 20, 30, 40, 50, and 60 mesh fractions can becombined in one sample that provides a uniform looking tablet with goodflow properties. The particle size of the granules used for the dualrelease and extended release tablets may be in the range of −20+40 mesh,−16+60 mesh, −20+60 mesh, or −20+50 mesh. The particle size of thegranules may be from about −8 mesh to about +150 mesh, particularly fromabout −10 mesh to about +80 mesh, and more particularly from about −20mesh to about +60 mesh.

Compressed tablets may be prepared by the application of high pressure,using steel punches and dies to powders or granulations. The basecomposition may be compressed into a tablet to form an extended releasetablet. In another embodiment, the cap composition may be compressedinto a tablet to form a quick release tablet. In a further embodiment,the base and cap composition can be layered and compressed into a tabletto form a dual release tablet with a base composition layer and a capcomposition layer. The base and the cap composition may be combined inany ratio. The ratio may be adjusted depending on the active ingredient.In yet another embodiment, the base composition and the cap compositionmay be combined and may contain different active ingredients.

The cap composition may be prepared by mixing the ingredients describedabove. The ingredients may be mixed in varying orders (see the examplesbelow).

In one embodiment, an individual tablet is pressed by first pouring thebase composition into a die of desired size and shape. The die may betapped to level the ingredients and the composition may be pressed withthe corresponding punch by hand to remove air to a uniform depth in thedie. This process may be used for a dual release or extended releasetablet. For a dual release tablet, the cap composition may be added tothe tablet by pouring it into the die on top of the base composition.The die may be again tapped to level and then the punch may be placed ontop of the cap and compressed using a hydraulic press. An Arbor pressmay be used to extract the tablet from the punch and die.

For commercial production, tablets may be prepared by a single stationpress or a multiple station or rotary tablet press. Examples of singlestation tablet presses include, without limitation, a Carver, Stokes,and Cadmach press. Examples of rotary tablet presses include, withoutlimitation, a Fette Perfecta Press, a Colton Press, an Adept EngineersPress, a Stokes Press, a Manesty Beta Press, a Key International Press,a Korsch Press, and a Courtoy Press. Both the dual release and theextended release tablets may be pressed to about 5,000 to about 40,000pounds, particularly to about 9,000 lbs to about 20,000 pounds, and moreparticularly about 10,000 to about 12,000 pounds. In one embodiment,small granules may be compressed under pressure using a punch and dieassembly tablet press.

For commercial production of tablets, a mixture comprising a plaster anda binder may be heated to form a solid without the use of water. Withheating, the glass transition temperature may be reached whereby thebinder may be in a pliable, soft, flexible, rubbery state (plasticized)and the plaster may impart hardness to the mixture. For commercialproduction, an Extrud-O-Mix mixer/extruder (for example, model EM-6 with15 hp motor; manufactured by Bepex International LLC, Minneapolis,Minn.) may be used. The mixer/extruder may be equipped with a jacket forheating and/or cooling in the mixing zone to plasticize the mixture byimparting heat and mechanical force. The end of the mixer/extruder maybe mounted with an orifice plate with small holes (for example, about0.5 mm to 3.0 cm, suitably about 0.5 mm to 1.5 mm diameter holes)through which the plasticized composition may be extruded to form longstrands. The strands may be immediately cooled and fed to an oscillatinggranulator. An oscillating granulator may break up the strands intosmaller pieces. The smaller pieces or granules may be fed to a separator(for example, a Sweco separator) to select for a particular granule size(for example, −20+60 mesh).

The compositions of the present invention may be compressed into a hard,dust-free tablet having an aesthetically pleasing waxy appearance. Thebase composition of the dual release tablet and the extended releasetablet may have a waxy-looking appearance and be almost dust-free. Thedual release and extended release tablets may be less chalky, haveincreased binding characteristics, and have less attrition and cleanerhandling. The dual release and extended release tablets may also possesspleasing aesthetic characteristics. In contrast, without the granulationand heat treatment, the base composition of the dual release andextended release tablets may appear chalky and may be dusty to thetouch.

The hardness of tablets may be tested by any standard method thatmeasures the fracturing/breaking point (compressive force) of a tablet.For example, an MHT-100 Portable Hardness Tester manufactured by thePharma Alliance Group (Valencia, Calif.) may be used. In one embodiment,the tablets may have a hardness of at least about 100 Newtons, at leastabout 200 Newtons, at least about 300 Newtons, or at least about 400Newtons.

In one embodiment the tablets may be round with beveled edges of varyingthickness and diameter. In another embodiment, the shape may beelongated so as to fit through grates on catch basins. The tablets maybe any shape or size desired depending on the selection of the punch anddie and the amount of fill material required to achieve the requisiteamount of active ingredient and the desired extended releasecharacteristics. As used herein, “tablet” forms include tabletsthemselves as well as other solid forms or shapes known in the art suchas sticks, pucks, briquettes, pellets, beads, spheres, granules,micro-granules, extrudates, cylinders, ingot, and the like. Any shapetablet may be used in accordance with the invention and is only limitedby the ingenuity of the tool and die maker.

Without being limited by theory, it is believed that the water-solublebinder combined with the plaster granulates just by heating and applyingmechanical force or mixing. Alternatively, the binder and plastergranulates upon heating with or without mixing and with or withoutapplying pressure. Within the temperature and mixing ranges disclosedherein, the powder may granulate without the addition of liquids. It isbelieved that the plaster, the active ingredient, and the water-solublebinder form a matrix. For example, in one embodiment, the water-solublebinder comprises polyethylene glycol and the plaster comprises plasterof Paris. When the base composition is placed in water, it is believedthat the polyethylene glycol dissolves and the plaster of Parishydrolyzes into gypsum. The gypsum matrix incorporates the activeingredient and is able to hold its shape, which provides the extendedrelease of the active ingredient over a period of time. Without beinglimited by theory, it is believed that the non-water soluble binder actsto slow down the rate at which the remaining matrix dissolves.

Without being limited by theory, it is believed that many activeingredients cannot be compressed directly into a tablet because theylack the proper characteristics of bonding or binding together.Therefore, additional ingredients such as binders, disintegrants, andlubricants may be added. Furthermore, plaster has been found to beuseful in controlling the release of active ingredients in the presenceof water.

The compositions of the present invention have sufficient density sothat they fill a die to be compressed into a tablet of a desired weight.The dual release tablets may weigh from about 0.5 grams to about 20.0grams, particularly from about 1.0 gram to about 10.0 grams, and moreparticularly from about 1.0 gram to about 5.0 grams. The extendedrelease tablets may weigh from about 1.0 gram to about 70 grams,particularly from about 2.5 grams to about 60.0 grams, and moreparticularly from about 5.0 grams to about 50 grams.

The dual release, extended release, and quick release tablets may beused by, for example, without limitation, placing the tablets in bodiesof water. The tablets may also be placed in an area that isintermittently wet. Examples of application sites include, withoutlimitation, marine and freshwater aquatic environments, storm waterdrainage areas, sewers and catch basins, woodland pools, snow pools,roadside ditches, retention ponds, freshwater dredge spoils, tiretracks, rock holes, pot holes and similar areas subject to holdingwater; natural and manmade aquatic sites, fish ponds, ornamental pondsand fountains, other artificial water-holding containers or tanks,flooded crypts, transformer vaults, abandoned swimming pools,construction and other natural or manmade depressions, stream eddies,creek edges, and detention ponds; freshwater swamps and marshesincluding mixed hardwood swamps, cattail marsh, common reed wetland,water hyacinth ponds, and similar freshwater areas with emergentvegetation; brackish water swamps and marshes, intertidal areas; sewageeffluent, sewers, sewage lagoons, cesspools, oxidation ponds, septicditches and tanks, animal waste lagoons and settling ponds, livestockrunoff lagoons, wastewater impoundments associated with fruit andvegetable processing, and similar areas. Other examples include, withoutlimitation, dormant rice fields (for application during the intervalbetween harvest and preparation of the field for the next croppingcycle), and in standing water within pastures/hay fields, rangeland,orchards, and citrus groves where mosquito breeding occurs.

In one embodiment, the base composition and the cap composition of thedual release tablets may be formed into a tablet that may be used inpotable water, which provides immediate release and extended release ofan active ingredient. In another embodiment, the extended releasecomposition may be formed into a tablet that provides a 30 day extendedrelease of an active ingredient. In another embodiment, the compositionmay be formed into a tablet that provides a 60 day extended release ofan active ingredient. In a further embodiment, the composition may beformed into a tablet that provides a 150 day extended release of activeingredient. In yet another embodiment, the tablets may be labeled“organic.”

The dual release, quick release, and extended release tablets may beused, without limitation, for plant protection (combating organismsharmful to plants or protecting plants from attack or infestation),controlling or eliminating pests, protecting organic and non-organicmaterials from pests, protection of animals against pests, watertreatment to increase the potability of water, and combinations thereof.Harmful organisms or pests may include, without limitation, weeds,fungi, insects, arachnids or nematodes, bacteria, parasites, protozoans,archaea, protests, amoeba, other microorganisms, and combinationsthereof. The tablets may be used to control or eliminate mosquitoes.Mosquitoes are vector agents that may carry disease-causing viruses andparasites, for example, from person to person. Mosquito borne diseasesinclude but are not limited to yellow fever, dengue fever, and malaria.Methods used to prevent the spread of disease may include methods ofcontrolling or eliminating mosquitoes. The tablets may be used incombination with, but not limited to, other pesticides, insecticides,fungicides, nematocides, acaricides, bactericides, algicides,herbicides, germicides, rodenticides, antioxidants, anti-preservatives,biocides, catalysts, chemical reactants, disinfectants, drugs, plantgrowth regulators, synergists, fertilizers, soil conditioners and/oranimal feeds, other agents that benefit the environment of use, andcombinations thereof. In one embodiment, the tablet may be used as awater treatment to remove undesired microorganisms. In anotherembodiment, tablets may remove other impurities and comprise otheractive agents including, but not limited to, sequestering agents orchelating agents for metal contamination, and flocculants to removesuspended particles. In one embodiment, the dual release, quick release,and extended release tablets are useful for the control of mosquitopopulations since mosquitoes require water to complete their life cycle.The dual and extended release tablets may provide extended release of anactive ingredient when placed in water, for example, during mosquitocontrol application.

EXAMPLES

Exemplary embodiments of the present invention are provided in thefollowing examples. These examples are presented to illustrate thepresent dual release, quick release, and extended release compositionsand to assist one of ordinary skill in making and using the same. Theexamples are not intended in any way to otherwise limit the scope of theinvention.

For the examples below, the technical material, Spinosad NT was suppliedby Dow AgroSciences LLC, Indianapolis, Ind. Spinosad NT consists of theactive ingredients Spinosyn A and Spinosyn D at a total nominalconcentration of 90.4%. It is derived from the metabolites of thenaturally occurring bacteria, Sacchararopolyspora spinosa and has beenshown to be highly effective against a wide variety of insects includingspecies from the orders Coleoptera, Diptera, Hymenoptera, Lepidoptera,and Thysanoptera. The plaster was supplied by United States GypsumCompany, Chicago, Ill. The polyethylene glycol was supplied by DowChemical Company, Midland, Mich. and sold under the trademark ofCarbowax. It is also available from various distributors and in varyingmolecular weights. The dicalcium phosphate dihydrate, the magnesiumstearate, the citric acid, and the sodium bicarbonate are commodityitems and are sold by various suppliers and/or distributors.

Example 1

Extended release tablets were made with the following formulationspresented in Table 1 and 2. The compositions were direct compressed on aCarver press at 15,000 lbs or direct compressed on a Stokes press at30,000 lbs.

TABLE 1 Extended release formulations. Component Sample 1 wt % Sample 2wt % Spinosad Technical (90.5) 0.552 2.76 No. 1 Moulding Plaster 0.5003.31 C-Base Plaster 4.098 25.60 Carbowax 8000 0.800 8.00 MagnesiumStearate 0.050 0.33 Total: 6.000 40.00

TABLE 2 Extended release formulations. Sample 1 Sample 2 Sample 3 Sample4 Component Wt % Wt % Wt % Wt % Spinosad Technical 5.25 5.30 5.60 5.6088.9% No. 1 Moulding Plaster 84.42 85.23 0.00 83.40 C-Base Plaster 0.000.00 83.40 0.00 Carbowax 1450 9.38 0.00 0.00 0.00 Carbowax 3350 0.009.47 10.00 10.00 Magnesium stearate 0.95 0.00 1.00 1.00 Total: 100.00100.00 100.00 100.00

Example 2

A dual release tablet comprising a cap and a base was made with theformulation set forth below in Tables 3 and 4. A cap provides quickrelease of an active ingredient, and the base provides an extendedrelease of an active ingredient.

TABLE 3 Base formulation. Component Grams Wt (%) Spinosad Tech (90.4%)0.100 9.452 C-Base Plaster 0.840 79.395 Carbowax 8000 0.100 9.452Dicalcium Phosphate Dihydrate 0.008 0.756 Magnesium Stearate 0.010 0.945Total: 1.058 100.000

TABLE 4 Cap formulation. Component Grams Wt (%) Spinosad Tech (90.4%)0.012 4.110 C-Base Plaster 0.050 17.123 Citric Acid 0.050 17.123 SodiumBicarbonate 0.150 51.370 Dicalcium Phosphate Dihydrate 0.030 10.274Total: 0.292 100.000

The total grams of material in one tablet were 1.350 grams. The baseformulation was heated and appeared to become denser and formedgranules. The cap and base ingredients were mixed separately and thendirectly compressed using a Carver tablet press.

Example 3

A method using heat treatment was developed to improve the flowabilityof the sample to the tablet press. A base formulation is set forth belowin Table 5.

TABLE 5 Base formulation. Component Grams Wt (%) Spinosad Tech (90.4%)0.100 9.452 C-Base Plaster 0.840 79.395 Carbowax 8000 0.100 9.452Dicalcium Phosphate Dihydrate 0.008 0.756 Magnesium Stearate 0.010 0.945Total: 1.058 100.000

The ingredients were added to a 250 mL beaker and then placed in a 75°C. water bath. The formulation was mixed with a spatula by hand duringheating. The formulation was heated at 75° C. for one hour, and then thetemperature was increased to 80° C. for 30 minutes. The batch did notharden. It remained soft and pliable and appeared to easily granulate.

The granules were screened using U.S.A. standard testing sieves, 8″diameter. The granulated sample was sieved through a 10, 20, 30, 40, 50,and 60 mesh screen.

Example 4

A dual release tablet that may be used in potable water was preparedusing +40 mesh heat treated base and a non-heat-treated cap. The capportion of the tablet comprised 0.29 grams and the heat-treated basecomprised 1.058 grams, for a total of 1.348 grams per tablet. The basewas poured into a 12 mm diameter beveled flat face die. The die wastapped to level out the base. The die was pressed by hand. The cap wasthen poured into the die and tapped to level. The die was pressed to10,000 pounds using a Carver Press, Model C and then released. An ArborPress 1/2T was used to extract the tablet. The tablet was then placed ina glass jar containing desiccant.

Example 5

Twenty tablets of 30 day extended release tablets were prepared forfield trials using the non-heated process and the heated process, withthe formulations presented in Tables 6 and 7, respectively. Each tabletweighed 6 g.

TABLE 6 Non-heated 30 day formulation. Component Wt (%) Grams SpinosadTech 9.403 18.806 No. 1 Moulding plaster 8.333% 16.666 C-Base Plaster68.098 136.196 Carbowax 8000 13.333 26.666 Magnesium Stearate 0.8331.666 Total: 100.00 200.00

The formulation was blended/ground in a Waring blender at high speed and80% power in one minute intervals for a total of 2 minutes. Each tabletweighed 6 g.

TABLE 7 Heated 30 day formulation Component Wt (%) Grams Spinosad Tech,88.6% 9.403 18.806 No. 1 Moulding plaster 8.333% 16.666 C-Base Plaster68.098 136.196 Carbowax 8000 13.333 26.666 Magnesium Stearate 0.8331.666 Total: 100.00 200.00

The ingredients were weighed into a 600 mL beaker and mixed with aspatula after the addition of each ingredient. The mixing cycles arepresented in Table 8. The mixture was poured into a Waring blender thatwas equipped with heating tapes (Thermolyne/Barnstead, Fibrox HeavyInsulated, 6 ft) that were wrapped around the stainless steel container.The temperature at the start of mixing was 65° C. on the outside.

TABLE 8 Mixing cycles. Mix Speed as (Heat) % of voltage TemperatureThermolyne Mix Cycle Mix Time regulator batch Input Control 1 2 min 80%63° C. #2 2 2 min 80% 63° C. #2 3 2 min 80% 63° C. #2 4 2 min 60% — #2 51 min 50% — #3 6 2 min 50% — #3 7 5 min 50% — #4 8 5 min 50% 57.8° C.  #5

The end temperature was 63° C. The sides of the mixer were scraped downbetween each mixing cycle. The speed was reduced and the top of themixer was kept off at cycle #5 where the powder was beginning togranulate. Mixing was stopped after cycle #8 as granules were startingto harden and increase in size.

A Wiley mill and a coffee grinder were used to reduce the particle sizeof large granules. The granules were screened through 20, 30, 40, 50,and 60 mesh and −60 mesh (pan) sieves (Table 9).

TABLE 9 Sieve analysis. Sieve Size Grams +20 mesh 10.12 +30 mesh 15.28+40 mesh 72.91 +50 mesh 20.75 +60 mesh  6.53 −60 mesh 48.14 (remainingin pan) Total: 86.87% recovery

Example 6

Twenty tablets of 150 day extended release tablets were prepared forfield trials using the non-heated process and the heated process, withformulations presented in Tables 10 and 11, respectively. Each tabletweighed 40 g.

TABLE 10 Non-heated 150 day formulation. Component Wt (%) Grams SpinosadTech 7.055 84.660 No. 1 Moulding plaster 8.275 99.300 C-Base Plaster64.340 772.080 Carbowax 8000 20.00 240.000 Magnesium Stearate 0.3303.960 Total: 100.00 1200.00

The ingredients were weighed into a KitchenAid® mixing bowl and mixedfor 5 minutes using a paddle stirrer at the #2 setting. The batch wasdivided into 300 gram increments and ground in a Waring blender at lowspeed and 96% powder for 2 cycles of 1 minute each. The mixture waspoured back into the KitchenAid® mixing bowl and mixed for 5 additionalminutes using a paddle stirrer at the #2 setting. The recovery was1186.8 grams, or 98.9%. 40 grams of powder was weighed out and pressedinto a tablet.

TABLE 11 Heated 150 day formulation. Component Wt (%) Grams SpinosadTech 7.055 84.660 No. 1 Moulding plaster 8.275 99.300 C-Base Plaster64.340 772.080 Carbowax 8000 20.00 240.000 Magnesium Stearate 0.3303.960 Total: 100.00 1200.00

Barnstead/Thermolyne (Fibrox, heavy insulated, 6 ft) heating tapes wereapplied to a KitchenAid® mixing bowl using Nashua® Extreme Weather foilbacked tape (rated to 260° F.). The mixing bowl was preheated (#3 onThermolyne input control, type 45500).

The ingredients were weighed separately and added to the mixing bowl.The temperature of the heating tape was at #3, or 60° C. Using a paddlemixer, the batch was mixed for 10 minutes on the “stir” cycle ofKitchenAid®. The batch temperature was 34.9° C. The mixing blade wasswitched to a wire whisk and the temperature was increased to #4 on theThermolyne input controller. The temperature was 79° C. The batch wasmixed for 10 minutes on the #2 cycle of KitchenAid®. The batchtemperature was 39° C. The temperature was increased to #5 on theThermolyne input controller and the mixing was continued on the #2cycle. The powder was turning to paste along the walls of the mixingbowl, so the sides were scraped about every 2 minutes of mixing. Thespeed of the mixing was slowly increased as the powder began togranulate. The total mixing time was approximately 1 hour.

The granules were screened through 20, 30, 40, 50, and 60 mesh sieves.The larger particles were ground in a Wiley mill and then re-sieved.

TABLE 12 Sieve analysis. To make a 40 gram tablet the following factionswere used % of sieved Sieve Size Grams (g/batch) gramules +12 mesh176.14 0.00 0.00 +20 mesh 274.54 150.15 28.14 +30 mesh 228.08 228.0842.74 +40 mesh 81.06 81.06 15.19 +50 mesh 54.31 54.31 10.18 +60 mesh28.00 20.00 3.75 −60 mesh 170.00 0.00 0.00 Total: 84.34% recovery 533.60100.00

The granules used for a 150 day tablet are described in Table 12 above.533.60 grams made 13 tablets.

Example 7

30 day extended release tablets were prepared as set forth below inTables 13-15. Each tablet weighed 6 g.

TABLE 13 30 day formulation. Component Wt (%) Grams Spinosad Tech, 88.6%9.403 28.209 No. 1 Moulding plaster 8.333 24.999 C-Base Plaster 68.098204.294 Carbowax 8000 13.333 39.999 Magnesium Stearate 0.833 2.499Total: 100.00 300.00

TABLE 14 Mixing cycles. Mix Speed as (Heat) % of voltage TemperatureThermolyne Mix Cycle Mix Time regulator batch Input Control Initial — —23.7° C. — (start at #3) 1 2 min 50% 52.4° C. #3 2 1 min 80% 55.8° C. #33 1 min 80% 59.1° C. #3 4 6 min 50% 63.2° C. #3

The formulation was sieved by hand (Table 15). The +30 and +40 meshfractions were mixed together and were used to press into 6 gram tabletshaving a 22 mm diameter.

TABLE 15 Sieve analysis. Sieve Size Grams +20 mesh 28.64 +30 mesh +40mesh 74.53 +50 mesh 29.24 +60 mesh 98.94 −60 mesh 64.27

Example 8

A 150 day extended release tablet was formulated as set forth below inTables 16-18. Each tablet weighed 40 g.

TABLE 16 150 day formulation. Component Wt (%) Grams Spinosad Tech,88.6% 7.055 32.275 No. 1 Moulding plaster 8.275 41.375 C-Base Plaster64.340 321.700 Carbowax 3350 20.000 100.000 Magnesium Stearate 0.3301.650 Total: 100.00 500.000

The ingredients were weighed into a 1 quart glass measuring containerand mixed by hand using a spatula. Mixing cycles are presented in Table17. The mixture was poured into a 1 liter stainless steel dry blendingcontainer that was equipped with heating tapes (Thermolyne/Barnstead,Fibrox heavy insulated, 6 ft) wrapped around the outer part of thecontainer. The mixture was mixed for a total of 2 minutes in 1 minuteintervals before heating was started. Half of the batch was processed ata time so as not to overload the mixer. 250 grams of powder were removedbefore heating.

TABLE 17 Mixing cycles. Mix Speed as (Heat) % of voltage TemperatureThermolyne Mix Cycle Mix Time regulator batch Input Control 1 2 min 80%48.4° C. #2 2 1 min 80% 52.8° C. #2 3 1 min 80% 56.9° C. #3 4 1 min 80%59.1° C. #3 5 6 min 50% 65.0° C. #3

The formulation was screened by hand, using 8″ diameter USA Standardtest sieves.

TABLE 18 Sieve analysis. Sieve Size Grams +16 mesh 22.77 +30 mesh +40mesh +50 mesh 117.44  −50 mesh 81.57 Total 221.78 (out of 250 = 88.71%)

Example 9

A 150 day extended release tablet was formulated as set forth below inTables 19-21.

TABLE 19 150-day formulation. Component Wt (%) Grams Spinosad Tech 7.05521.165 USG #1 Molding plaster 8.275 24.825 C-Base Plaster 64.340 193.020Carbowax 3350 20.000 60.000 Magnesium Stearate 0.330 0.990 Total: 100.00300.000

To make a 40 gram tablet at 6.25%, 200 grams were needed. Two 300 grambatches were prepared.

The ingredients were weighed into a 600 mL beaker and blended with aspatula after the addition of each ingredient. Mixing cycles arepresented in Table 20. The mixture was poured into a 1 liter stainlesssteel Waring blender (old model with no handle) that was equipped withheating tapes as described in Example 8. Heating was not started untilafter 1 minute of mixing. The formulation was sieved by hand (Table 21).

TABLE 20 Mixing cycles. Mix Speed as (Heat) % of voltage TemperatureThermolyne Mix Cycle Mix Time regulator batch Input Control 1 1 min 100%36.4° C. 0 2 1 min 110% 44.3° C. Start at #2 3 1 min 110% 52.3° C. #2 41 min 110% 58.6° C. #2

TABLE 21 Sieve analysis. Sieve Size Grams +16 mesh 98.68 +30 mesh +40mesh +50 mesh 126.91 −50 mesh 47.66 Total 273.25 (out of 300 = 91.08%)

Example 10

A 150 day extended release tablet was formulated as set forth below inTables 22-24.

TABLE 22 150 day formulation Component Wt (%) Grams Spinosad Tech, 88.6%7.055 21.165 No. 1 Moulding plaster 8.275 24.825 C-Base Plaster 64.340193.020 Carbowax 3350 10.000 30.000 Carbowax 8000 10.000 30.000Magnesium Stearate 0.330 0.990 Total: 100.00 300.000

To make a 40 gram tablet at 6.25%, 200 grams were needed, thereforeanother 300 gram batch was prepared.

The ingredients were weighed into a 600 mL beaker and blended with aspatula after the addition of each ingredient. The mixture was pouredinto a 1 liter stainless steel Waring blender that was equipped withheating tapes as described in Example 8.

TABLE 23 Mixing cycles. Mix Speed as (Heat) % of voltage TemperatureThermolyne Mix Cycle Mix Time regulator batch Input Control 1 1 min110%  36.1° C. 0 2 1 min 110%  41.0° C. Start at #2 3 1 min 45% 45.6° C.#2 4 1 min 45% 53.8° C. #2 5 Continuous 45% 59.6° C. #3 6 While 45%62.0° C. #3 granulatingg

TABLE 24 Sieve analysis. Sieve Size Grams +16 mesh 39.24 +30 mesh +40mesh +50 mesh 169.79 −50 mesh 31.68 Total 240.71 (recovery = 80.24%)

Example 11

A 200 gram sample of the dual release tablet base (which may be used forpotable water) and a 30 day tablet were prepared as set forth in Tables25 and 26, respectively, to measure the physical properties.

TABLE 25 Dual release tablet base. Grams/ Component Wt (%) tabletgms/batch Spinosad Tech, 88.6% 9.639 0.102 19.28 C-Base Plaster 79.2080.838 158.42 Carbowax 8000 9.452 0.100 18.90 Dicalcium PhosphateDihydrate (DCP) 0.756 0.008 1.51 [Magnesium Stearate] 0.945 0.010 1.89Total: 100.00 1.058 200.00

The C-Base, Spinosad, Carbowax, and DCP were weighed into a 1 literstainless steel Waring blender. The blender was run for 30 seconds onrheostat at 70%. The sides were scraped down and the blender was run foran additional 30 seconds. Recovery was 196.74 grams per 198.11 grams, or99.31%.

TABLE 26 30 day tablet. Grams/ Component Wt (%) tablet Gms/batchSpinosad Tech, 88.6% 9.403 0.564 18.81 USG #1 Molding Plaster 8.3330.500 16.67 C-Base Plaster 68.098 4.086 136.20 Carbowax 8000 13.3330.800 26.67 [Magnesium Stearate] 0.833 0.050 1.67 (not added) Total:100.00 6.000 200.00

The C-Base, Spinosad, and Carbowax were weighed into a 1 liter stainlesssteel waring blender. The blender was run for 30 seconds on rheostat at70%. The sides were scraped down and the blender was run for anadditional 30 seconds. Recovery was 197.33 grams per 198.33 grams, or99.50%.

Example 12

An extended release tablet was prepared as set forth below in Tables27-30.

TABLE 27 Base formulation. Component Wt (%) Grams/tablet Spinosad Tech(88.60%) 9.369 0.102 C-Base Plaster 79.208 0.838 Carbowax 8000 9.4520.100 Dicalcium Phosphate Dihydrate 0.756 0.008 Magnesium Stearate 0.9450.010 Total: 100.00 1.058

TABLE 28 Cap formulation. Component Wt (%) Grams/tablet Spinosad Tech(88.60%) 4.223 0.0122 C-Base Plaster 16.423 0.0476 Citric Acid 17.2510.0500 Sodium Bicarbonate 51.753 0.1500 Dicalcium Phosphate Dihydrate10.350 0.0300 Total: 100.00 0.2898

The cap was prepared first (Table 28). Inert ingredients were stored at50° C. except for technical material. Each ingredient was weighed into a1 liter stainless steel waring blender and mixed for 30 seconds(rheostat=30, blender=#7). The sides of the blender were wiped down andthe formulation was mixed for another 30 seconds and the sides wereagain wiped down. A final mix was conducted for 1 minute (rheostat=50,blender=#7). The mixture was poured into an eight ounce wide mouth jar.The recovery was 115.44 grams per 115.92 grams of the batch, or 99.59%.

Next, the heat treated base was prepared (Table 27). The ingredientswere weighed into a 600 mL beaker and mixed with a spatula. The mixturewas poured into a 1 liter stainless steel waring blender that wasequipped with heating tapes (Thermolyne/Barnstead, Fibrox heavyinsulated, 6 ft) that were wrapped around the blender. The blendedpowders were poured into the blender and heating was started.

TABLE 29 Mixing cycles. Mix Speed as (Heat) % of voltage TemperatureThermolyne Mix Cycle Mix Time regulator batch Input Control Initial — —  24° C. #3 1 2 min 80% 53.8° C. #3 2 1 min 80% 61.0° C. #3 3 1 min 80%63.0° C. #2 4 8 min 50% 63.2° C. #2 5 5 min 50% 63.2° C. #3

TABLE 30 Sieve analysis. Sieve Size Grams +12 mesh 3.99 +20 mesh 101.67+30 mesh 89.83 +40 mesh 51.01 +60 mesh 19.56 −60 mesh 21.93 Total 284.00(out of 300 = 94.67%)

A base sample was prepared using the +30 mesh, +40 mesh, and +60 mesh,for a total of 160.40 grams.

The cap sample was stored in the 50° C. oven when not in use. The basesample was stored at room temperature. The tablet was prepared asfollows. A complete tablet (assay should be 7.50%±5%) included 0.29grams of the cap sample and 1.058 grams of the base sample for a totalof 1.348 grams. The tablet was made by pouring the base into a 12 mmdiameter beveled flat face die. The die was tapped to level out the basepowder and was pressed by hand. The cap was poured into the die on topof the base and tapped to level. It was pressed to 10,000 pounds using aCarver Press (model C s/n 34000/486) and then released. An Arbor Press(½ ton) was used to extract the tablet. The tablets were placed in aglass jar containing desiccant. Assay cap powder was 3.78% (target3.74%) and the assay base granules were 8.67% (target 8.54%).

Example 13

A 45 pound batch of base was prepared as set forth below in Tables 31-32using a Ribbon Blender (Ross Model RB 42A-1 s/n 39786).

TABLE 31 Base formulation. Component Wt (%) 45 lb batch Spinosad Tech(88.60%) 9.66 4.35 C-Base Plaster 79.18 35.63 Carbowax 8000 9.45 4.25Dicalcium Phosphate Dihydrate 0.76 0.34 Magnesium Stearate 0.95 0.43(hold) Total: 100.00 45.00

The Spinosad, Carbowax, and DCP were weighed into small containers andpreheated in a 45° C. oven. The C-Base plaster was weighed into a 5gallon pail. The plaster was poured into a 1.0 cubic foot Charles RossRibbon blender (Model RB 42A-1, s/n 39786). Before loading the blender,Thermo Scientific Brisk Heat Heating tapes with controller were tapedonto the sides. The size was 1 inch wide by 10 feet long. A thermometerwas taped on the inside front and the back side and heating measurementswere taken to ensure the correct heat could be obtained (60° C.-63° C.).

The heat tapes appeared to provide enough heat for granulation of thebase powder. Only one set of heat tapes was used. The ribbon blender wasemptied.

TABLE 32 Temperatures. 2:00 pm Load blender, heat tape at 50% ofcontroller 2:45 pm Batch temp was 40° C. This was not enough heat, sothe outside heaters were mounted at the back and front of the mixer andput at the highest setting. 2:55 pm Batch temp was 47° C. The heat tapewas increased to 100% of the controller 3:15 pm Batch temp was 51° C.3:30 pm Batch temp was 56.5° C. 3:45 pm Batch temp was 58° C. 4:00 pmBatch temp was 59.3° C. (small clumps formed on the left and rightcorners) 4:15 pm Batch temp was 60.3° C. (beginning to granulate somixing was continued until 4:45 pm, then discontinued and the sample wasdischarged).

The +10 mesh fraction was sieved off and run through a hammer mill,Bantam Mikro Pulverizer (Type CF s/s, s/n 72-J-1322) without a screen toreduce larger sized particles. Then the sample was screened using a −20and a +60 mesh sieve to use for tabletting. 5.1 lbs was used to make thesample. This was multiplied by 0.95% for the Mg stearate amount. 22.15grams of Mg stearate were dusted onto this −20+60 mesh sample using a 50mesh sieve and mixed in a 8% quart stainless steel beaker.

Example 14

A 50 pound batch of base (30 day tablet) was prepared using a RibbonBlender. The blender was equipped with a set of heating tapes on eitherside (front and back). The tapes were Thermo Scientific, Brisk Heatheating tapes (controller s/n 89659/4).

A 30 day tablet (6 grams) was prepared as follows in Tables 33-35.

TABLE 33 Base formulation. Component Wt (%) 50 lb batch Spinosad Tech(88.60%) 9.50 4.8 No. 1 Moulding plaster 8.33 4.2 C-Base Plaster 68.0034.0 Carbowax 8000 13.33 6.7 Magnesium Stearate 0.83 0.4 (sprinkle onafter ingredients mixed) Total: 100.00 50.00

The C-Base plaster, No. 1 Moulding plaster, and Carbowax were weighedinto a 5 gallon pail (inerts). The tech was weighed into a 2.5 gallonpail and placed in a 50° C. oven. The temperature of the inerts was 24°C. They were poured into a Ross 1.0 cubic foot ribbon blender, ModelRB42A-1. The temperature of the tech was 25° C. It was poured into theblender and mixing was begun. The heating tapes were set at 35% of thecontrol. After 15 minutes of mixing, the mixer was stopped and thetemperature was 28° C. After 30 minutes of mixing, the mixer was stoppedand the temperature was 38° C. The temperature of the heat tapes wasincreased to 45% of the control. After 45 minutes of mixing, the mixerwas stopped and the temperature was 43° C. The sides were scraped with a1.5″ paint brush. The batch was still in the powder state. After 60minutes of mixing, the mixer was stopped and the temperature was 47° C.The sides were brushed down. The temperature of the heat tapes wasincreased to 50% of the control. After 1.5 hours the temperature was 56°C. There was some observable melting appearing in the front corner ofthe blender. The temperature of the heating tapes was lowered to 45% ofcontrol. The batch appeared to be densifying after 1.5 hours mixing and56° C. After an additional 10 minutes, the temperature of the heatingtapes was turned down to 35% of control, then 10 more minutes of mixing,followed by scraping of the sides. The temperature was lowered to 15% ofcontrol. After 10 additional minutes the temperature was lowered to 5%of control as the sample had begun densifying and sticking to the farwall of the blender. After 10 more minutes, the blender was stopped, thesides scraped down, the heating stopped, and a cooling fan was appliedto the back of the blender. The batch was allowed to cool with mixingfor approximately 15 minutes, then the mixing was stopped and clumpswere broken up (product warm, but not hot). The product was dischargedinto 2 trays. Recovery was 98.99%. There was some material left in theblender that had adhered to the walls. The larger, possibly unusablechunks were sieved off The first cut was to sieve off all sample thatwas +4 mesh using 8″ diameter sieves that were screened by hand.

Tablets were made using the −20+60 mesh fraction (23.68 lbs). See Table34 for sieve analysis. 0.83% of magnesium stearate was added so that thetablet would not stick in the tablet press. It was sifted onto thesample using a 50 mesh screen. A 6 gram tablet (beveled edge), 25 mmwide by 6.5 mm deep, was made using an Adept Engineers Rotary TabletPress

TABLE 34 Sieve analysis of the 50 lb batch of 30 day granules. SieveSize Pounds % +4 mesh 15.22 31.28 +10 mesh 9.57 19.67 +20 mesh 11.1622.94 −60 mesh 1.18 2.43 −20 +60 mesh 11.52 23.68 Total 48.65 100

773 tablets were made with 143.82 grams of powder left over and 28tablets were made at initial start up to define the parameters of thetablet press.

The sieve analysis for the granulated base is as follows in Table 35:

TABLE 35 Sieve analysis. Sieve Size Pounds % +4 mesh 24.84 58.57 +10mesh 1.17 2.76 −10 +20 mesh 1.61 3.80 +20 mesh 2.73 6.44 −60 mesh 6.9616.41 −20 +60 product 5.1 12.02 Total 42.41 100.00

The cap (0.29 grams) was prepared as follows in Table 36. The materialswere stored in a 45° C. oven to keep them dry.

TABLE 36 Cap formulation. Component Wt (%) Grams per batch Spinosad Tech(88.60%) 4.23 27.50 C-Base Plaster 16.42 106.72 Citric Acid 17.25 112.13Sodium Bicarbonate 51.75 336.38 Dicalcium Phosphate Dihydrate 10.3567.28 Total: 100.00 650.00

The ingredients were weighed into a 1 liter stainless steel Waring dryblending container. The batch was blended at the highest speed in 30second intervals. After each interval the sides were scraped down. Themixture was blended for 5 intervals, and then poured into a 1 quart widemouth glass jar. Recovery was 641.17 g or 99.56%.

A scored, bi-layer tablet was then made. 1.058 grams of the base werecombined with 0.29 grams of the cap for a 1.348 gram tablet. An AdeptEngineers 23 station rotary tablet press was used to make the tablet.

Example 15

A 50 pound batch of extended release tablet (150 day) was prepared tomake 40 gram tablets as in Table 37.

TABLE 37 Base formulation. Component Wt (%) Pounds per batch SpinosadTech(88.60%) 7.10 3.6 No. 1 Moulding plaster 8.27 4.1 C-Base plaster64.30 32.2 Carbowax 8000 20.00 10.0 Magnesium stearate 0.33 0.2(sprinkled on after ingredients mixed) Total: 100 50.0

The C-Base, molding plaster, and Carbowax (inerts) were weighed into a 5gallon pail and placed in a 45° C. oven to preheat overnight. TheSpinosad was weighed into a 4 quart pail and placed in a 45° C. oven inthe morning (the technical material was not preheated overnight). Theinerts were loaded into a Ross Ribbon Blender, 1.0 cubic foot, equippedwith a set of Thermo Scientific Brisk Heat heating tapes with controlleron the back and front of the outside of blender, each measuring 1″ wideby 10′ long). The temperature of the inerts in the oven was 42° C. Thetemperature of the Spinosad in the oven was 37° C. The inerts were addedto the blender and mixed for 5 minutes, and then the Spinosad was addedand mixed for 2 more minutes. Heating was then begun. The temperature ofthe batch was 30° C. The heat tapes were set at 25° C. After 15 minutesof heating and mixing, the batch temperature was measured to be 34° C.and the sides were scraped down. After 30 minutes of heating and mixingthe batch temperature was 35° C. The heat tape setting was increased to50%. After 45 minutes of heating and mixing the batch temperature was40° C. After 60 minutes of heating and mixing the batch temperature was48° C. After 1.5 hours of heating and mixing the batch temperature was52° C. After an additional 15 minutes, the batch was beginning todensify. The mixer was intermittently turned off and the walls werescraped down. The mixer shut down due to excessive torque requirementson the motor. The batch was not entirely granulated, however, the largerchunks (+4 mesh) were screened off using the 8″ diameter sieves.

Recovery of the +4 mesh particles was as follows in Table 38:

TABLE 38 Recovery. +4 mesh 12.28 lbs 24.59% −4 mesh 37.66 lbs 75.41%Total 49.94 lbs  100%

Next, the +20 mesh particle size was screened off using an 8″ diametersieve. 21.18 lbs were recovered.

The −20 mesh fraction, weighing 21.18 pounds was sieved to remove thefines. The fines for this product was −60 mesh and weighed 9.75 lbs.

Final tabulation of the sample is as follows in Table 39.

TABLE 39 Sieve analysis. +4 mesh 12.28 lbs −4 mesh This fraction, whichwas 37.66, was sieved again so there was no remaining fraction. It wascontained within the +20 mesh +20 mesh 16.40 lbs −20 mesh 21.18 lbs(this fraction was sieved to remove fines) −20 +60 mesh product 12.17lbs

This provided a total amount of 12.16 pounds of granulated/heatedproduct which could make about 138 tablets (at 40 grams/tablet).

Example 16

TABLE 40 Cap formulation. Component Wt (%) Grams per batch Spinosad Tech(88.60%) 4.23 27.50 C-Base Plaster 16.42 106.72 Citric Acid 17.25 112.13Sodium Bicarbonate 51.75 336.38 Dicalcium Phosphate Dihydrate 10.3567.28 Total: 100.00 650.00

The cap formulation was mixed according to Table 40. The cap sample wasplaced into a 170×90 Pyrex crystallizing dish in a 50° C. oven overnightto ensure the sample was dry.

TABLE 41 Base formulation. Component Wt (%) Grams per batch SpinosadTech (88.60%) 9.66 28.98 C-Base Plaster 79.18 237.54 Carbowax 8000 9.4528.35 DCP 0.76 28.35 Magnesium stearate 0.95 2.85 Total 100.00 300.00

The ingredients were weighed into a 600 mL beaker and mixed with aspatula. They were poured into a 1 liter stainless steel Waring blenderequipped with heating tapes (Thermolyne/Barnstead Fibrox HeatingInsulated, 6 ft) that were wrapped around the blender and secured withExtreme Weather 330 foil backed tape. The blended powders were pouredinto the Waring blender and heating was begun. Mixing cycles arepresented in Table 42.

TABLE 42 Mixing cycles. Mix Speed as (Heat) % of voltage TemperatureThermolyne Mix Cycle Mix Time regulator batch Input Control Initial — —22.6° C. — 1  2 min 80% 45.1° C. #3 2  1 min 80% 57.0° C. #3 3 30 sec80% 58.9° C. #3 4 30 sec 80% 63.5° C. #3 5 30 sec 80% 64.8° C. #3

While the sample was still warm and most of the powder had becomegranular, it was screened through a 20 mesh sieve, forced throughopenings with hand pressure. Recovery: The +20 mesh material was placedback in a 50° C. oven. −20+60 mesh=181.35 grams. −60 mesh was 15.55grams.

The tablet was prepared by mixing 0.29 grams of the cap sample (Table40) with 1.058 grams of the similarly-prepared base (Table 41) to make a1.348 gram tablet. The base was poured into a 12 mm beveled flat facedie. The die was tapped to level out the base sample and was pressed byhand. The cap was poured into the die on top of the base and tapped tolevel. It was pressed to 10,000 pounds using a Carver press (Model C,s/n 34000/486), then released and an Arbor Press (½ ton model) was usedto extract the tablet. The tablets were placed in a glass jar containingdesiccant packs.

Example 17

30 day extended release tablets were prepared as follows. Three batchesof 300 grams each were made and then combined into a single batch. Themagnesium stearate was added to the single batch.

A 30 day tablet (6 grams) was prepared as follows in Table 43.

TABLE 43 Base formulation. Component Wt (%) Grams/batch Spinosad Tech(88.60%) 9.40 28.21 No. 1 Moulding plaster 8.33 25.00 C-Base Plaster68.10 204.29 Carbowax 8000 13.33 40.00 Magnesium Stearate 0.83 2.50(sprinkle on after ingredients mixed and pregranulated) Total: 100.00300.00

The ingredients were weighed into a 600 mL glass beaker and mixed with aspatula after the addition of each ingredient. They were poured into a 1liter stainless steel Waring blender that was equipped with heatingtapes (Thermolyne/Barnstead, Fibrox heavy insulated, 6 ft) that werewrapped around the blender and secured to the sides with high heat tape.The tablets were prepared as described above in Example 6. Therecoveries were as follows in Table 44.

TABLE 44 Recovery. Batch 1 Batch 2 Batch 3 Totals −16 +60 mesh 199.49 g 227.87 g  192.28 g  614.64 g (product) +16 mesh 70.51 g 19.82 g 72.15 g162.48 g (overs) −60 mesh (fines) 13.53 g 35.59 g 27.84 g  76.96 g %recovery 94.51% 92.76% 97.42% 94.90% (total) % recovery 66.50% 74.29%64.09% 68.29% (product)

All of the product (−16+60 mesh) was poured into a 9″×13″ glass Pyrexdish and dusted with Mg stearate using a 30 mesh hand sifter. 4.92 gramsof Mg stearate were used. The tablets (6 gms each) were pressed with aCarver Press C at 8000 lbs using a flat face die.

Example 18

Eight batches (Tables 45 and 46) of base were made for a potable watertablet base (1.058 grams). The nominal concentration was 8.54% (range8.113% to 8.967%), and a 2% excess was added to ensure the activeingredient was within the specification. Magnesium stearate was addedafter granulation.

Batch 1

TABLE 45 Batch 1 Base formulation. Component Wt (%) lbs/batch SpinosadTech (88.60%) 9.83 5.41 C-Base Plaster 79.02 43.46 Carbowax 8000 9.455.20 DCP 0.76 0.42 Magnesium stearate (not 0.95 0.52 added) Total:100.00 55.00

The C-Base plaster was weighed into a 5 gallon pail. The Spinosad wasweighed into a 6 liter pail, the Carbowax into a 4 quart pail and theDCP into an 800 mL tri-cornered polypropylene beaker. Half of the amountof plaster was charged to the Ribbon blender and then the Spinosad, theCarbowax, and the DCP were charged. Finally, the remaining half of theplaster was charged. The mixer top was covered and the ingredients mixedfor 20 minutes. The mixture was discharged at the bottom of the mixer byopening the gate valve. The discharge container was not large enough andmuch of the sample was lost. Recovery was 51.74 pounds.

Batches 2-8

Batches 2-8 were made using the following procedure. The C-Base plasterwas weighed into a 5 gallon pail. The Spinosad was weighed into a 6liter pail, the Carbowax into a 4 quart pail, and the DCP into an 800 mLtri-cornered polypropylene beaker. Half of the amount of plaster wascharged to the Ribbon Blender and then the Spinosad, the Carbowax, andthe DCP were charged. Finally, the remaining half of the plaster wascharged. The mixer top was covered and the ingredients mixed for 20minutes. The mixture was discharged at the bottom of the mixer byopening the gate valve. The mixture was discharged into a 14 gallon,21″L×15″ W plastic container. Once all of the sample was discharged fromthe blender into a 14 gallon container, it was poured into a 30 gallonfiber drum that was lined with 2 bags of polyethylene. Approximately 150lbs of the sample was placed into each of three fiber drums.

TABLE 46 Batches 2-8 Base formulations. Component Wt (%) grams lbs/55 lbbatch Spinosad Tech 9.83 0.102 5.41 (88.60%) C-Base Plaster 79.01 0.83843.46 Carbowax 8000 9.45 0.100 5.20 DCP 0.76 0.008 0.42 Magnesiumstearate 0.95 0.010 0.52 (not added) Total: 100.00 1.058 55.00

Example 19

Eight batches (Table 47) of base with 55 lbs per batch were made for a30 day tablet (6 grams). The nominal active ingredient was 8.33% (range7.91% to 8.75%), and a 2% excess was added to ensure the activeingredient was within the specification. Magnesium stearate was addedafter the formation of granules.

The batches were prepared using the following method. The C-Base plasterwas weighed into two 5 gallon pails, the #1 Molding plaster was weighedinto a 4 quart pail, the Carbowax into two 4 quart pails, and theSpinosad into a 6 liter pail. One of the pails of the C-Base plaster wascharged into a Ribbon Blender (Model RB-42-A-1, s/n 39786), then theSpinosad was charged, followed by the Carbowax, the #1 Molding plaster,and the remainder of the C-Base plaster. The mixer top was covered andthe ingredients mixed for 20 minutes. The mixture was discharged into a14 gallon, 21″L×15″W plastic container. Once all of the sample wasdischarged from the blender into the 14 gallon container, the sample waspoured into a 30 gallon fiber drum that was lined with 2 polyethylenebags. The target was 150 pounds per drum.

TABLE 47 Batches 1-8 formulations. Component Wt (%) lbs/batch SpinosadTech (88.60%) 9.59 5.27 No. 1 Moulding Plaster 8.33 4.58 C-Base Plaster67.91 37.35 Carbowax 8000 13.33 7.33 Mg Stearate (not added) 0.83 0.46Total: 100.00 55.00 *Note: Because Mg stearate is not added, activeingredient = 8.57%.

Example 20

A 30 day extended release tablet is prepared as follows in Table 48. Thepre-mixed powder is dry granulated using heat (60-63° C.) and mixing toimprove flowability to the tablet press. The granules are screened to aparticle size range of −20+40 mesh. The formulation is as follows:

TABLE 48 Formulation. Ingredient Approximate Weight % Active ingredient9% No. 1 Moulding plaster 8% Carbowax 8000 13%  USG Hydrocal C-baseplaster 69%  Magnesium stearate added 1% post granulation Total 100% 

Example 21

A dual release tablet, which may be used for potable water, is preparedas follows in Table 49. The pre-mixed powder is dry granulated usingheat (60-63° C.) and mixing to improve flowability to the tablet press.The granules are screened to a particle size range of −20+40 mesh. Theformulation is as follows:

TABLE 49 Formulation Ingredient Approximate Weight % Active ingredient10% DCP  1% Carbowax 8000 10% USG Hydrocal C-base plaster 78% Magnesiumstearate added  1% post granulation Total 100% 

Example 22

A dual release tablet that may be used for potable water as described inone of the previous examples is placed into a 200 liter water container.The tablet is expected to control mosquito larvae. One tablet is usedper 200 liters of water. Multiple tablets are used when water volumeexceeds 200 liters at a rate equivalent to 1 additional tablet for each200 liter volume increase. A new tablet is used every 60 days or asneeded. More frequent treatments are made if monitoring indicates thatlarval populations have reestablished, or water consumption has renderedinitial treatments ineffective. The tablet is also applied as a spottreatment to areas where mosquitoes are breeding at rates appropriate tosite size (water volume).

Example 23

A 30 day, 60 day, or 150 day tablet as described in one of the previousexamples is used to control mosquito and midge larvae. The tablet isexpected to provide up to 30 days, 60 days, or 150 days of residualcontrol. The tablet is applied prior to flooding, on snow and ice inbreeding sites prior to spring thaw, or at any time after flooding inlisted sites. The treatment is continued through the last brood of theseason. The 150 day tablet may last through the entire mosquito seasonor up to 180 or 170 days, whichever is shorter. The tablet is unaffectedin dry down situations and begins working again during subsequentwetting events.

For mosquito control in non-(or low-) flow, shallow depressions (up to 2feet in depth), the depression is treated on the basis of surface areaby placing 1 tablet per 100 square feet. The tablet is placed in thelowest areas of mosquito breeding sites to maintain continuous controlas the site alternately floods and dries up.

Storm water drainage areas, sewers and catch basins are treated byplacing 1 tablet into each catch basin. For application sites connectedby a water system, i.e., storm drains or catch basins, all of the waterholding sites in the system are treated to maximize the efficiency ofthe treatment program.

For application to small contained sites which may not be amenable to arate of a single tablet per 100 square feet, 1 tablet per contained site(e.g., cesspools and septic tanks, transformer vaults, abandoned pools,and other small artificial water-holding containers) is used.

Example 24

An MHT-100 Portable Hardness Tester manufactured by the Pharma AllianceGroup (Valencia, Calif.) was used to measure the hardness of a 6 gram,25 mm diameter tablet according to one of the formulations presentedabove. The average hardness of this tablet was determined to be 439.6Newtons. The tablet was found to be very strong when compared toconventional tablets and products manufactured by, for example, a moldedplaster slurry process.

We claim:
 1. A method for forming a composition comprising mixingwithout adding water at least one active agent, a plaster, and a binder,wherein the composition provides an extended release of the active agentover a period of at least 30 days when placed in water.
 2. The method ofclaim 1, the method further comprising heating during the mixing step.3. The method of claim 1, wherein mixing without adding water comprisesdry-blending.
 4. The method of claim 1, wherein the binder comprises awater-soluble binder.
 5. The method of claim 4, wherein thewater-soluble binder comprises polyethylene glycol.
 6. The method ofclaim 4, wherein the composition further comprises at least oneadditional component selected from a non-water-soluble binder and alubricant.
 7. The method of claim 6, wherein the plaster comprisesPlaster of Paris, the water-soluble binder comprises polyethyleneglycol, the non-water-soluble binder comprises dicalcium phosphatedehydrate, the lubricant comprises magnesium stearate, and the activeagent comprises at least one of a pesticide, insecticide, herbicide,fungicide, nematicide, acaricide, bactericide, rodenticide, miticide,algicide, germicide, repellant, and nutrient.
 8. The method of claim 6,wherein the active agent is present in an amount of about 0.01-50% wt,the plaster is present in an amount of about 40-90% wt, thewater-soluble binder is present in an amount of about 5-50% wt, thenon-water-soluble binder is present in an amount of about 0-30% wt, andthe lubricant is present in an amount of about 0-1.5% wt.
 9. A methodfor forming a composition comprising mixing without water at least oneactive agent, a plaster, and a binder, wherein the composition providesa quick release of the active agent over a period of less than 10minutes when placed in water.
 10. The method of claim 9, the methodfurther comprising heating during the mixing step.
 11. The method ofclaim 9, wherein mixing without adding water comprises dry-blending. 12.The method of claim 9, wherein the binder comprises a non-water-solublebinder.
 13. The method of claim 9, wherein the active agent comprises atleast one of a pesticide, insecticide, herbicide, fungicide, nematicide,acaricide, bactericide, rodenticide, miticide, algicide, germicide,repellant, and nutrient.
 14. The method of claim 12, wherein thecomposition further comprises at least one additional component selectedfrom a disintegrating agent, a water-soluble binder, and a lubricant.15. The method of claim 14, wherein the disintegrating agent comprisesan effervescent.
 16. The method of claim 15, wherein the plastercomprises Plaster of Paris, the water-soluble binder comprisespolyethylene glycol, the non-water-soluble binder comprises dicalciumphosphate dehydrate, the lubricant comprises magnesium stearate, and thedisintegrating agent comprises at least one of citric acid and sodiumbicarbonate or combinations thereof.
 17. The method of claim 14, whereinthe active agent is present in an amount of about 0.01-30% wt, theplaster is present in an amount of about 0-40% wt, the disintegratingagent is present in an amount of about 20-80% wt, and thenon-water-soluble binder is present in an amount of about 2-40% wt. 18.A method of making an extended release solid matrix, the methodcomprising: a) mixing at least one active agent, a plaster, and a binderto form a mixture; and b) heating the mixture at about 40° C. to about75° C.
 19. The method of claim 18, wherein the mixture of step (b) ispliable.
 20. The method of claim 18, the method further comprisingapplying a mechanical force to the mixture to form granules; andcompressing the granules into a tablet.
 21. The method of claim 18, themethod further comprising: c) cooling the mixture; d) breaking up thecooled mixture into granules; and e) compressing the granules into atablet.
 22. The method of claim 21, wherein step (d) is performed byforcing the cooled mixture through an oscillating granulator.
 23. Themethod of claim 21, wherein the tablet is produced by a dry granulationprocess.
 24. The method of claim 21, wherein a pressure of 5,000 to30,000 pounds is applied to the granules in step (e).
 25. The method ofclaim 21, the method further comprising screening the granules for aparticle size from about −20 mesh to about +60 mesh before step (e). 26.The method of claim 18, the method further comprising: c) forcing themixture through an extruder and cooling to form cooled extrudates; d)breaking up the cooled extrudates into granules; and e) compressing thegranules into a tablet.
 27. The method of claim 26, wherein a pressureof 5,000 to 30,000 pounds is applied to the granules in step (e). 28.The method of claim 26, the method further comprising screening thegranules for a particle size from about −20 mesh to about +60 meshbefore step (e).